Patients with schizophrenia and other psychotic disorders with disease onset typically during adolescence and early adulthood have a variety of functional disabilities that can profoundly influence educational attainment, work objectives, and social interactions, even if medication can control positive symptoms.

Most intervention studies thus far have focused on prevention of progression to psychosis, but it's increasingly being recognized that models are needed that can identify patients most likely to experience deterioration in functioning.

To explore possible predictive factors, they enrolled 92 patients considered at high risk because of positive scores on the Scale of Prodromal Symptoms, along with 68 healthy controls, following them for a mean of 3 years.

Baseline assessments involved measurement of multiple components of neurocognitive ability, including language, executive function, and attention, while social and role function evaluations considered peer and family relationships and performance in school or at work.

During the follow-up period, 47.8% of patients had poor social outcomes and 48.9% had poor role outcomes.

In addition, 32.6% had poor outcomes in both, while 35.9% had good outcomes for both.

In a multivariate analysis of neurocognitive factors and functional outcome, there were significant differences on all eight domains. The largest difference in effect size was for processing speed (f=0.46, P<0.001).

There also was a significant group effect for role outcome, with the largest difference in effect size being in verbal memory (f=0.47, P<0.001).

For the final regression model that identified the strongest predictors for social outcomes, the area under the curve was 0.824 (95% CI 0.736-0.913, P<0.001). The "optimal" sensitivity and specificity were 72.7% and 75%, respectively.

For the final model for role outcomes, the area under the curve was 0.77 (95% CI 0.68-0.87, P<0.001), while "optimal" sensitivity and specificity were 62.2% and 72.3%, respectively.

A total of 15 patients developed psychosis during follow-up. The predictors of role outcome (verbal memory, motor disturbances, and baseline role functioning) were independent of psychosis, but development of psychosis was significantly associated with poor social outcome (OR 8.74, 95% CI 1.30-58.78, P=0.03).

"These findings add to a growing body of evidence that cognitive heterogeneity is present prior to the onset of the illness and could be used as a differential predictor of functional as well as psychotic outcomes," the researchers noted.

Certain of the predictive factors seemed to influence specific components of functioning, they explained.

One example was for processing speed and social outcomes. "Slowing in understanding and reaction to incoming information might be debilitating in multiple domains of real-world functioning, such as the ability to select and maintain conversational topics," they suggested.

In contrast, verbal memory was a central factor in role outcome, as this is necessary for academic or occupational success.

"Taken together, these results support the presence of an underlying developmental vulnerability core for the illness that is thought to be the major source of later functional difficulties, independent of emerging positive symptoms," they concluded.

Further research will be needed to more fully confirm the validity of these models. Carrion's group plans to study the effects of pharmacologic interventions on social and role outcomes for patients at risk.

Limitations of the study included a lack of data on other potentially important factors such as "social cognition" and stigma.

The study was supported by the National Institute of Mental Health and Zucker Hillside Hospital.

The authors have received fees and support from various organizations, including Merck, GlaxoSmithKline, Actelion, AstraZeneca, Eli Lilly, Novartis, Pfizer, Takeda, Teva, the National Alliance for Research in Schizophrenia and Depression, and the National Institute of Mental Health.

Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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